FIGURE 1.

CR3 and SRA advance the phagocytosis of degenerated myelin by promoting the activation of paxillin and cofilin whereas SIRPα inhibits phagocytosis by promoting the inactivation of paxillin and cofilin (a schematic representation of the working hypothesis). Degenerated myelin ligates simultaneously phagocytic receptors CR3 and SRA and immune inhibitory receptor SIRPα. CR3 and SRA produce the signaling that culminates in structural changes (marked by ellipses); filopodia and lamellipodia first engulf the myelin-debris as they extend and then pull-in the myelin-debris as they retract. We hypothesize the following. Phagocytic receptors promote paxillin activation through phosphorylation (paxillin → p-paxillin) leading to cofilin activation through dephosphorylation (p-cofilin → cofilin). In turn, cofilin promotes the production of filopodia and lamellipodia and so phagocytosis is advanced. In contrast, SIRPα promotes the inactivation of paxillin through p-paxillin dephosphorylation (p-paxillin → paxillin) leading to cofilin inactivation through phosphorylation (cofilin → p-cofilin). In turn, the production of filopodia and lamellipodia is reduced and so phagocytosis is inhibited. Retraction of filopodia and lamellipodia is promoted by MLCK triggering motor activity in non-muscle-myosin which then initiates F-actin/non-muscle-myosin-based contraction (not illustrated). Dashed lines mark indirect interactions; blue lines mark activation and red lines inhibition of phagocytosis.